Ziprasidone

Second-generation antipsychotics
Second-generation antipsychotics

A second-generation antipsychotic for schizophrenia and bipolar mania that prolongs the QT interval. Taken with food; never with other QT-prolonging drugs.

Updated Nov 12, 2026

Quick facts

Group: Second-generation antipsychotics
Target: Dopamine D2 and serotonin 5-HT2A receptors; also binds the noradrenaline transporter (shown)
Used for: Schizophrenia in adults · Manic or mixed episodes
Key effects: Sleepiness · Dizziness on standing · Nausea
Monitor: Baseline potassium and magnesium · Weight
ATC: N05AE04

No doses: the clinician sets them by the current guideline.

Mechanism of action

Dopamine D2 and serotonin 5-HT2A receptors; also binds the noradrenaline transporter (shown)Ziprasidone

The figure shows ziprasidone bound to the human noradrenaline transporter, a secondary target; its main antipsychotic targets are the D2 and 5-HT2A receptors.

Target in 3D: Dopamine D2 and serotonin 5-HT2A receptors; also binds the noradrenaline transporter (shown). PDB structure 8WTY (RCSB PDB, public domain). View the structure at RCSB PDB

Ziprasidone blocks dopamine D2 and serotonin 5-HT2A receptors, reducing psychotic symptoms and mania with fewer extrapyramidal effects than first-generation drugs. It also binds the noradrenaline transporter (the structure shown). It delays cardiac repolarisation and prolongs the QT interval, which is why other QT-prolonging drugs are contraindicated.

Blocks D2 and 5-HT2A receptors
Also binds the noradrenaline transporter
Psychosis and mania settle
Delays cardiac repolarisation: longer QT

Indications

Schizophrenia in adults Schizophrenia →
Manic or mixed episodes of bipolar I disorder, and maintenance with lithium or valproate Bipolar disorder →

Adverse effects

Common

Sleepiness, headache, restlessness
Dizziness on standing
Nausea, constipation or diarrhoea
Runny nose, cough
Raised prolactin: breast changes, missed periods

Contraindications

History of QT prolongation, including congenital long QT syndrome
Recent acute myocardial infarction or uncompensated heart failure
Other QT-prolonging drugs (for example dofetilide, sotalol, quinidine, pimozide, moxifloxacin, pentamidine)

Key interactions

QT-prolonging drugs: Additive QT prolongation and arrhythmia; contraindicated.
Diuretics or anything causing low potassium or magnesium: Raises the risk of torsades de pointes.
Alcohol and CNS depressants: More drowsiness.

What is monitored

Baseline potassium and magnesium, corrected before starting
ECG when there are cardiac risks; stopped if the QTc stays markedly prolonged
Rash with fever or swollen glands
Weight, glucose and lipids

Administration and safety

Oral capsule twice a day with food, swallowed whole.
Every new medicine is checked for QT prolongation.
An intramuscular form exists for acute agitation in hospital.

Pregnancy and breastfeeding

Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; it may also cause problems in breastfed infants.

Nursing care

Before: check potassium, magnesium and the cardiac history.
During: report palpitations, fainting or dizziness at once.
Watch the skin for rash, blisters or mouth sores with fever.
Teach to take with meals and to rise slowly.

Pharmacokinetics

Absorption: Oral capsule; food roughly doubles absorption. An intramuscular form is used for acute agitation.

Test yourself

Think of the answer, then tap the question to see it.

Which ECG change limits ziprasidone use?

QT prolongation, with a risk of torsades de pointes.

Which two electrolytes are checked before starting it?

Potassium and magnesium.

What must be checked in every other medicine before ziprasidone is started?

Whether it also prolongs the QT interval; such combinations are contraindicated.

Add to my cards (3)

Connections

← Back to the class: Second-generation antipsychotics

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Ziprasidone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ZIPRASIDONE HYDROCHLORIDE capsule (DailyMed (U.S. National Library of Medicine), 2021); Cryo-EM structure of noradrenaline transporter in complex with ziprasidone (RCSB Protein Data Bank, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.